Mechanism of action
Antiepileptic drug of prolonged action. It shows antiepileptic activity in all types of epilepsy.
Valproates are believed to increase the concentration of gamma-aminobutyric acid in the CNS by inhibiting the GABA-transferase enzyme.
Suction
Bioavailability of the drug is about 100%.
Compared with other oral forms of the drug, the prolonged form is characterized by the absence of latent absorption time, prolonged absorption, a more linear correlation between dose and plasma concentration, lower (by about 25%), but relatively more stable plasma concentration between 4 h and 14 h, which allows to obtain a more uniform concentration of valproic acid during the day.
Distribution
Valproate sodium penetrates the BBB.
The therapeutic efficacy of the drug is manifested at a plasma concentration of 40 to 100 mg / l. When the concentration of the active substance in the plasma exceeds 200 mg / l, it is necessary to reduce the dose. It penetrates the placental barrier and is excreted in breast milk in an insignificant amount (1-10% of the total plasma concentration).
With regular use of Css set for 3-4 days of therapy.
Metabolism and excretion
Does not induce cytochrome P enzymes450. Excreted mainly in the urine in conjugated form. T1/2 is 8-20 hours
Indications and usage
- treatment of generalized or partial epilepsy, especially for the following types of seizures: absences, myoclonic, tonic-clonic, atonic;
- partial epilepsy: simple or combined seizures, secondary generalized seizures;
- specific syndromes (Vesta, Lennox-Gasto);
- treatment and prevention of bipolar affective disorders.
The dose should be set in accordance with the age and weight of the patient, taking into account the individual sensitivity to the drug.
For adults at the beginning of treatment, the drug is prescribed in a dose of 10-15 mg / kg of body weight, then it is titrated to the optimal dose. As a rule, the optimal dose of Depakene Chrono is 20-30 mg / kg body weight per day. If necessary, you can increase the dose to 50 mg / kg body weight and above, but it requires careful monitoring of the patient's condition.
Children over 3 years old The average dose is approximately 30 mg / kg / day.
Elderly patients do not require special correction of the dosage regimen.
In patients taking other anticonvulsant drugs, treatment with the drug is started gradually, so as to achieve a clinically effective dose in about 2 weeks. Then begin the gradual abolition of other anticonvulsants.
Patients who have not received prior treatment with other anticonvulsants, the dose of Depakene Chrono should be increased gradually, with an interval of 2-3 days, so as to achieve a clinically effective dose after 1 week.
Features dosage forms allow you to take the drug 1 time / day.
In the treatment of manic syndrome in bipolar affective disorders, the drug is prescribed in the same doses as in epilepsy.
Adverse reactions
Gastrointestinal: nausea, epigastric pain; rarely, liver dysfunction; in extremely rare cases, pancreatitis.
From the side of the central nervous system: blurred consciousness, lethargy, isolated stuporous states; in very rare cases - reversible dementia, isolated reversible parkinsonism, hearing loss.
Hemic and lymphatic: thrombocytopenia; rarely - anemia and leukopenia, pancytopenia.
With sides of the blood coagulation system: in some cases, more often when used in high doses, a decrease in the level of fibrinogen or an increase in bleeding time.
Allergic reactions: in some cases, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme.
Other: isolated and moderately pronounced hyperammonemia; in some cases - hair loss (this side effect is temporary and / or dose-dependent), weight gain, amenorrhea, impaired menstruation, vasculitis, Fanconi syndrome.
Contraindications
- acute hepatitis;
- chronic hepatitis;
- cases of active hepatitis in the family history, primarily of medicinal genesis;
- hepatic porphyria;
- Hypersensitivity to the drug.
Pregnancy and breastfeeding
The general risk of developmental malformations when taking valproate in the first trimester of pregnancy is not higher than that of other antiepileptic drugs. Cases of facial dysmorphy are described; in rare cases, multiple malformations, especially of the extremities (the frequency of development of such effects has not yet been precisely established); violation of the development of the embryonic neural tube: myelomeningocele, spina bifida (the frequency of such complications is 1-2%).
If a woman is planning a pregnancy, the indications for antiepileptic treatment should be reviewed; recommend to consider additional prescription of folic acid.
When pregnancy should not be interrupted by antiepileptic treatment with valproate, if it is effective. In such cases, monotherapy is recommended; The minimum effective daily dose should be divided into several doses.
When using the drug during pregnancy, a special examination is necessary to identify any abnormalities in the development of the fetus.
Individual cases of hemorrhagic syndrome have been described in newborns whose mothers took sodium valproate during pregnancy; the onset of the syndrome is associated with hypofibrinogenemia.In newborns, platelet count, plasma fibrinogen levels should be monitored, coagulation tests and coagulation factors should be performed.
Sodium valproate is excreted in breast milk in small quantities (from 1% to 10% of plasma concentration). According to clinical observations, to date, in the neonatal period, children (who were breastfed while their mothers took sodium valproate) did not develop any marked clinical adverse symptoms.
Special notes
Before starting therapy, before surgery, if spontaneous hematomas or bleeding occur, it is recommended to monitor the pattern of peripheral blood (counting the number of platelets), determine the bleeding time and conduct coagulation tests.
Periodic monitoring of liver function is necessary before starting treatment and during the first 6 months of therapy.
When detecting a small increase in the activity of liver enzymes, especially at the beginning of treatment, it is recommended to carry out a more complete laboratory examination (including, in particular, the determination of the prothrombin index) in order to correct the regime if necessary; further examination should be repeated.
With a significant decrease in the prothrombin index, especially in combination with a decrease in the level of fibrinogen, blood clotting factors, an increase in the level of bilirubin and transaminases, treatment with the drug should be suspended. If the patient receives salicylates at the same time, they should be canceled immediately.
In extremely rare cases, severe liver damage may develop (during the first 6 months of treatment). Patients should be warned of the need to immediately notify the physician of the occurrence of the following symptoms: non-specific symptoms, usually appearing suddenly, such as asthenia, anorexia, severe fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; recurrence of seizures in patients with epilepsy. In the event of the onset of these symptoms, an immediate examination of liver function is necessary.
The risk of developing severe pancreatitis is increased in patients with severe epileptic seizures, neurological symptoms, while carrying out complex anticonvulsant therapy. In patients with concomitant abnormal liver function, the risk of death of severe pancreatitis increases. In acute abdominal pain syndrome, an immediate examination of the patient is necessary, and when the diagnosis of pancreatitis is confirmed, the drug should be withdrawn.
In young children, the risk of developing pancreatitis is very high.
When using Depakene Chrono in patients with renal insufficiency, it may be necessary to reduce the dose of the drug.
If it is necessary to administer the drug to patients with systemic lupus erythematosus and other diseases of the immune system, the expected therapeutic effect and the possible risk of therapy should be assessed, since when using Depakene Chrono in extremely rare cases, there were violations of the immune system.
If a carbamide cycle enzyme deficiency is suspected, metabolic studies should be carried out prior to the initiation of drug therapy because of the risk of hyperammonemia.
If necessary, the simultaneous use of the drug Depakin Chrono and phenobarbital recommend monitoring the patient's condition during the first 15 days of joint therapy with immediate reduction of the dose of phenobarbital when a sedative effect appears and determining the concentration of phenobarbital in the blood plasma if necessary.
Symptoms: coma, muscular hypotonia, hyporeflexia, miosis, dysfunction of respiration.
Treatment: gastric lavage, if after taking the drug has passed no more than 10-12 hours; providing osmotic diuresis; monitoring and correction of the functional state of the cardiovascular system. If necessary, carry out dialysis.
With the simultaneous use of Depakene Chrono with neuroleptics, antidepressants, MAO inhibitors, benzodiazepines, their pharmacological action can be enhanced.
When combined, the drug Depakene Chrono increases the concentration of phenobarbital in the blood plasma.
With the simultaneous use of Depakin Chrono increases the concentration of primidone in the blood plasma and enhances the side effects of primidone (including sedative). If necessary, the use of such a combination is recommended careful monitoring of the patient's condition (especially at the beginning of therapy).
With simultaneous use of Depakene Chrono with phenytoin, a decrease in the total concentration of phenytoin is observed with an increase in the concentration of its free form, which can cause symptoms of overdose.
With the simultaneous use of Depakene Chrono can enhance the toxic effect of Carbamazepine .
When combined, Depakene Chrono can slow down the biotransformation of lamotrigine and increase it.1/2, and also increases the likelihood of skin rash.
With the simultaneous use of Depakin Chrono can increase the concentration of zidovudine in the blood plasma, which leads to increased toxicity of zidovudine.
With simultaneous use with Depakin Chrono, antiepileptic drugs that induce microsomal liver enzymes (phenytoin, phenobarbital, carbamazepine) can reduce the concentration of valproic acid in the blood plasma.
With the combined use of felbamate and Depakene Chrono, it is possible to increase the concentration of valproic acid in the blood plasma.
The combined use of Depakene Chrono and mefloquine may increase the biotransformation of valproic acid and, as a result, the development of seizures.
With simultaneous use of Depakene Chrono and drugs that bind tightly to plasma proteins (eg, acetylsalicylic acid), it is possible to increase the concentration of free valproic acid in the blood plasma.
With simultaneous use of Depakene Chrono with cimetidine or Erythromycin, it is possible to increase the concentration of valproic acid in the blood plasma due to a decrease in its biotransformation in the liver.
The drug should be stored in a dry place at room temperature. Shelf life - 3 years.
Pharmacy sales terms
The drug is available on prescription.
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